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The mechanism of RNR irreversible inhibition by tezacitabine starts by its conversion into tezacitabine diphosphate 2.6, which, similarly to the natural substrate of the reaction, undergoes H-3' abstraction by Cys-439, leading to a radical that is stabilized by delocalization onto the adjacent C=C double bond (structure 2.7). The subsequent evolution of this radical has been studied through theoretical calculations, and the mechanistic pathway that has been proposed to be the major one is summarized in Fig. 2.9.10 The main steps involved are nh2

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